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GFPT1 高表达预示可切除胰腺导管腺癌患者预后不良。

High GFPT1 expression predicts unfavorable outcomes in patients with resectable pancreatic ductal adenocarcinoma.

机构信息

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No.270 DongAn Road, Shanghai, 200032, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

出版信息

World J Surg Oncol. 2021 Jan 31;19(1):35. doi: 10.1186/s12957-021-02147-z.

DOI:10.1186/s12957-021-02147-z
PMID:33517899
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7849098/
Abstract

BACKGROUND

Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Therefore, we investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC.

METHODS

We analyzed public datasets to compare GFPT1 expression in tumor tissues and normal/adjacent pancreatic tissues. We measured the relative GFPT1 expression of 134 resected PDAC specimens in our institution, using real-time polymerase chain reaction (PCR). Survival was compared between high and low GFPT1 expression groups using Kaplan-Meier curves and log-rank tests. Multivariate analyses were estimated using Cox regression and logistic regression models.

RESULTS

GFPT1 is generally upregulated in PDAC tissues, according to the analysis of public datasets. The data from our institution shows that high GFPT1 expression was correlated with a high rate of lymph node (LN) metastasis (p = 0.038) and was an independent risk factor for LN metastasis (odds ratio (OR) = 3.14, 95% confidence interval (CI) = 1.42 to 6.90, P = 0.005). High GFPT1 expression was significantly associated with poor overall survival (OS; P = 0.019) in patients with resected PDAC. The multivariable-adjusted hazard ratio (HR) for mortality when comparing patients with high and low GFPT1 expression was 2.54 (95% CI = 1.35 to 4.79, P = 0.004).

CONCLUSIONS

GFPT1 is generally upregulated in PDAC tissue and is associated with a high risk of LN metastasis and an unfavorable outcome in patients with resectable PDAC, suggesting its crucial role in PDAC progression.

摘要

背景

谷氨酰胺果糖-6-磷酸转氨酶 1(GFPT1)是己糖胺生物合成途径(HBP)的第一个限速酶,在胰腺导管腺癌(PDAC)的进展中起着关键作用。因此,我们研究了 GFPT1 表达在可切除 PDAC 患者中的预后意义。

方法

我们分析了公共数据集,以比较肿瘤组织和正常/相邻胰腺组织中的 GFPT1 表达。我们使用实时聚合酶链反应(PCR)测量了我们机构 134 例切除的 PDAC 标本中的相对 GFPT1 表达。使用 Kaplan-Meier 曲线和对数秩检验比较高和低 GFPT1 表达组的生存情况。使用 Cox 回归和逻辑回归模型进行多变量分析。

结果

根据公共数据集的分析,GFPT1 在 PDAC 组织中通常上调。我们机构的数据表明,高 GFPT1 表达与淋巴结(LN)转移率高相关(p=0.038),并且是 LN 转移的独立危险因素(优势比(OR)=3.14,95%置信区间(CI)=1.42 至 6.90,P=0.005)。高 GFPT1 表达与可切除 PDAC 患者的总生存(OS)显著相关(P=0.019)。比较高和低 GFPT1 表达患者的多变量调整后的死亡风险比(HR)为 2.54(95%CI=1.35 至 4.79,P=0.004)。

结论

GFPT1 在 PDAC 组织中普遍上调,与 LN 转移风险高和可切除 PDAC 患者预后不良相关,提示其在 PDAC 进展中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/7849098/9a3798215a71/12957_2021_2147_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/7849098/869231e00ec7/12957_2021_2147_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/7849098/3bee348d3a97/12957_2021_2147_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/7849098/5ca89d8fd8c1/12957_2021_2147_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/7849098/9a3798215a71/12957_2021_2147_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/7849098/869231e00ec7/12957_2021_2147_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/7849098/3bee348d3a97/12957_2021_2147_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/7849098/5ca89d8fd8c1/12957_2021_2147_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b3/7849098/9a3798215a71/12957_2021_2147_Fig4_HTML.jpg

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